One of the most dynamic areas of modern cell biology is the study of the functions of calcium ions inside cells. Calcium is already known to control the contraction of all known types of muscle, the secretion of hormones from gland cells and transmitters from nerve synapses, plus a multitude of other functions (see Campbell, 1983). Calcium is also suspected, but not yet proven, to be at the center of some of the biggest remaining mysteries in biology, e.g., how a cell decides when to grow and divide, how non-muscle cells control their own movements, and how the nervous system stores learned patterns and memories. For example, the two most recent theories of the molecular mechanism of neuronal learning (see Kandel, 1981 and Lynch, et al., 1984) differ in most aspects but agree in postulating that minute localized fluctuations in cytostolic free calcium levels inside nerve synapses are the key link between long-term biochemical changes and the efficiency of information transfer at those synapses. To study these important physiological processes, it would be extremely useful to produce similar fluctuations in free calcium levels by independent experimental means. This would show to what extent the natural events could be mimicked or elicited in response to properly controlled calcium changes.
The present invention describes novel compounds that store Ca.sup.2+ in a physiologically inactive form until illuminated with ultraviolet light, whereupon the Ca.sup.2+ tends to be released and is free to activate physiological processes. The use of light to control the release offers tremendous advantages because the intensity, position, spatial extent, and duration of a light beam can be conveniently manipulated with great precision. By contrast, the only general means previously available for raising Ca.sup.2+ inside cells was to administer certain antibiotics extracted from fungi. These drugs, for example A23187 and ionomycin, act by transporting Ca.sup.2+ across cell membranes, but cannot be controlled in precise locale and duration of action, and have major toxic side effects.
The need for photolabile Ca.sup.2+ chelators of the type disclosed herein has been acknowledged by scientific investigators. For example, in a recent review of physiological and pharmacological manipulations with light flashes, Lester and Nerbonne (see Lester, et al., 1982) discuss both the need for such photolabile substances and their own unsuccessful attempts to synthesize a photosensitive chelator comprised of a photoisomerizable azobenzene group and an known calcium chelator such as EDTA and EGTA.